Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance
Author(s)
Type
Journal Article
Abstract
Solid tumours have oxygen gradients and areas of near and almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors and were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 and HT29; rectal cancer: HT55, SW837 and VACO4S) maintained in hypoxia (1 and 0.2% oxygen) compared with normoxia (20.9%). CRC cell lines also showed altered amino acid metabolism in hypoxia and hypoxia-responsive miRNAs were predicted to target genes in four metabolism pathways: beta-alanine; valine, leucine, iso-leucine; aminoacyl-tRNA; and alanine, aspartate, glutamate. MiR-210 was increased in hypoxic areas of CRC tissues and hypoxia-responsive miR-21 and miR-30d, but not miR-210, were significantly increased in 5-FU resistant CRCs. Treatment with miR-21 and miR-30d antagonists sensitized hypoxic CRC cells to 5-FU. Our data highlight the complexity and tumour heterogeneity caused by hypoxia. MiR-210 as a hypoxic biomarker, and the targeting of miR-21 and miR-30d and/or the amino acid metabolism pathways may offer translational opportunities.
Date Issued
2017-04-15
Date Acceptance
2017-02-13
Citation
Human Molecular Genetics, 2017, 26 (8), pp.1552-1564
ISSN
0964-6906
Publisher
OUP
Start Page
1552
End Page
1564
Journal / Book Title
Human Molecular Genetics
Volume
26
Issue
8
Copyright Statement
© The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/
4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000400911900014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
CARBONIC-ANHYDRASE-IX
CHEMORADIOTHERAPY IN-VITRO
TUMOR HYPOXIA
GENE-EXPRESSION
POOR-PROGNOSIS
RECTAL-CANCER
BREAST-CANCER
CELLS
CHEMOTHERAPY
THERAPY
Publication Status
Published
Date Publish Online
2017-02-16